The primary goals of this Mentored Career Development award are to develop the knowledge, skills, and experience necessary to progress to an independent researcher. The proposed career development plan combines basic science courses, didactic clinical research sessions, laboratory research, and mentored learning to ensure a facile transition to independence. Structured coursework will provide a solid foundation of knowledge while mentored proposal enactment will encourage hypothesis driven research and independent thinking. The New York University Medical Center will provide a rich academic environment with a diverse group of scientists in basic and clinical translational research and multiple core facilities and resources to support the state-of-the-art technologies and science within the institution. Within this environment, I will have the mentorship of Drs. Derya Unutmaz and William Borkowsky to provide the guidance necessary to develop into a successful researcher. The proposed research study is aimed to dissect the mechanisms and consequences of immune activation in HIV infected children. Although immune activation is a poor prognostic factor in both adults and children, we postulate that stimulation of an immature immune system differs in its mechanisms and consequences compared with adults and contributes to rapid disease progression in children. The specific goals are to determine: 1) Immunologic and microbial correlates of immune activation in HIV infected children;and 2) whether immune activation leads to T cell exhaustion in HIV infected children. We will examine novel T cell subsets, Th17 and T regulatory cells, and immunologic factors affecting activation that are largely unexplored in HIV infected children. An understanding of the immunological basis of T cell activation during HIV infection opens the possibility of identifying novel biomarkers or immunotherapies. Public Health Relevance: The proposed research will evaluate the effects of HIV on the immune system in HIV infected children. An understanding of how immune responses contribute to HIV disease progression may lead to vaccine development or novel immunotherapies.